1,721,048 research outputs found
Neuropilin-1 as therapeutic target for malignant melanoma
Full text linkNeuropilin-1 (NRP-1) is a transmembrane glycoprotein that acts as a co-receptor for various members of the VEGF family. Its ability to bind or modulate the activity of a number of other extracellular ligands, such as class 3 semaphorins, TGF-β, HGF, FGF and PDGF, has suggested the involvement of NRP-1 in a variety of physiological and pathological processes. Actually, this co-receptor has been implicated in axon guidance, angiogenesis and immune responses. NRP-1 is also expressed in a variety of cancers (prostate, lung, pancreatic or colon carcinoma, melanoma, astrocytoma, glioblastoma and neuroblastoma), suggesting a critical role in tumor progression. Moreover, a growing amount of evidence indicates that NRP-1 might display important functions independently of other VEGF receptors. In particular, in the absence of VEGFR-1/2, NRP-1 promotes melanoma invasiveness, through the activation of selected integrins, by stimulating VEGF-A and metalloproteinases secretion and modulating specific signal transduction pathways. This review is focused on the role of NRP-1 in melanoma aggressiveness and on the evidence supporting its use as target of therapies for metastatic melanoma
In vitro inactivation of human O6-alkylguanine DNA alkyltransferase by antitumor triazene compounds
No full textThe cytotoxic and mutagenic properties of antitumor triazene compounds (TZC) have been mainly attributed to their ability to form DNA adducts at the O6 position of guanine. Repair of these lesions is mediated by O6-alkylguanine DNA alkyltransferase (OGAT) in an autoinactivating reaction. Therefore when lesion repair has occurred, cells are depleted of OGAT until synthesis of new enzyme molecules takes place. In this study, we have evaluated the ability of DNA alkylated by different TZC to deplete OGAT activity. Moreover, we have also investigated whether these compounds might inactivate the OGAT enzyme by a direct reaction with the protein. Human OGAT protein was partially purified from insect cells infected with a recombinant baculovirus containing the human OGAT coding sequences. Thereafter human OGAT protein was exposed directly to TZC or to TZC-alkylated DNA. Among the TZC tested, p-(3-methyl-1-triazeno)benzoic acid was the most effective OGAT inactivator by direct interaction with the protein. Moreover DNA substrates treated with methylating TZC, such as temozolomide or p-(3-methyl-1-triazeno)benzoic acid, were more effective in depleting the repair enzyme, compared to DNA pretreated with the chloroethylating TZC mitozolomide. In conclusion, our results show that TZC inactivate in vitro OGAT activity by either direct or indirect mechanisms. Therefore TZC are good candidates for 1) increasing their own cytotoxicity, if used according to appropriate dose and treatment schedules and 2) reversing tumor cell resistance to O6-guanine alkylating agents
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Approaching coronavirus disease 2019: Mechanisms of action of repurposed drugs with potential activity against SARS-CoV-2
Full text linkOn March 11, 2020, the World Health Organization (WHO) declared the severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) a global pandemic. As of July 2020, SARS-CoV-2 has infected more than 14 million people and provoked more than 590,000 deaths, worldwide. From the beginning, a variety of pharmacological treatments has been empirically used to cope with the life-threatening complications associated with Corona Virus Disease 2019 (COVID-19). Thus far, only a couple of them and not consistently across reports have been shown to further decrease mortality, respect to what can be achieved with supportive care. In most cases, and due to the urgency imposed by the number and severity of the patients’ clinical conditions, the choice of treatment has been limited to repurposed drugs, approved for other indications, or investigational agents used for other viral infections often rendered available on a compassionate-use basis. The rationale for drug selection was mainly, though not exclusively, based either i) on the activity against other coronaviruses or RNA viruses in order to potentially hamper viral entry and replication in the epithelial cells of the airways, and/or ii) on the ability to modulate the excessive inflammatory reaction deriving from dysregulated host immune responses against the SARS-CoV-2. In several months, an exceptionally large number of clinical trials have been designed to evaluate the safety and efficacy of anti-COVID-19 therapies in different clinical settings (treatment or pre- and post-exposure prophylaxis) and levels of disease severity, but only few of them have been completed so far. This review focuses on the molecular mechanisms of action that have provided the scientific rationale for the empirical use and evaluation in clinical trials of structurally different and often functionally unrelated drugs during the SARS-CoV-2 pandemic
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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